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Case Reports
. 2021 Nov 5:9:752878.
doi: 10.3389/fped.2021.752878. eCollection 2021.

Tubuloglomerular Disease With Cone-Shaped Epiphyses Associated With Hypomorphic Variant and a Novel p.Cys14Arg in the TTC21B Gene: A Case Report

Martin Bezdíčka  1 , Dana Zemková  2 , Sylva Skálová  3 , Eva Hovorková  4 , Miroslav Podhola  4 , Jan Burkert  5 , Jakub Zieg  2
Affiliations
Case Reports

Tubuloglomerular Disease With Cone-Shaped Epiphyses Associated With Hypomorphic Variant and a Novel p.Cys14Arg in the TTC21B Gene: A Case Report

Martin Bezdíčka et al. Front Pediatr. .

Abstract

Monogenic nephrotic syndrome (NS) is associated with a resistance to initial glucocorticoid therapy and causative variants, which may be found in several genes influencing podocyte stability and kidney development. The TTC21B gene, which encodes the retrograde intraflagellar transport protein IFT139, is found mostly in association with ciliopathies in humans. The role of this protein in podocyte cytoskeleton stability was confirmed later and the mutated TTC21B also may be associated with proteinuric diseases, such as nephrotic syndrome. Our patient manifested as an infant with brachydactyly, nephrotic-range proteinuria, and renal tubular acidosis, and a kidney biopsy revealed focal segmental glomerulosclerosis (FSGS). Multiple phalangeal cone-shaped epiphyses of the hand were seen on X-ray. Next-generation sequencing revealed the well-described p.Pro209Leu heterozygous variant and a novel heterozygous p.Cys14Arg variant in the TTC21B gene. Our finding confirmed that the causative variants in the TTC21B gene may contribute to a spectrum of clinical features, such as glomerular proteinuric disease with tubulointerstitial involvement and skeletal abnormalities.

Keywords: TTC21B; case report; cone-shaped epiphyses; nephrotic syndrome; podocyte; proteinuria.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Hand X-ray image. Full arrows show coned epiphyses. Dashed arrows show the premature closure growth plates due to coned epiphyses.
Figure 2
Figure 2
Two heterozygous TTC21B variants found in the patient. Sequencing of maternal sample revealed p.Pro209Leu heterozygous variant, but not the novel p.Cys14Arg variant. The image was obtained by Geneious Prime software (Biomatters, Ltd., New Zealand).
Figure 3
Figure 3
Clinical course of the patient.
See this image and copyright information in PMC

References

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